FAK,文库林和塔林控制机制对YAP核定位敏感
Elijah N Holland1, Marc A Fernández-Yagüe2, Dennis W Zhou3
1Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Biomaterials
|March 28, 2024
概括
焦点粘附通过控制YAP的核定位来调节细胞行为. 破坏素-氨酸相互作用会降低核大小和YAP活性,而FAK抑制会影响YAP,不论核大小如何.
科学领域:
- 细胞生物学 细胞生物学
- 机械生物学 机械生物学
- 分子信号传输的方法
背景情况:
- 焦点粘附 (FAs) 对于机械传导至关重要,它将细胞外基质与细胞骨连接起来.
- 脂肪酸调节转录协激活剂的核转位和激活,即与YAP相关的蛋白质 (YAP).
- 通过FA蛋白控制YAP局部化的确切机制尚不清楚.
研究的目的:
- 研究素,塔林和焦粘附激酶 (FAK) 中特定功能域在调节YAP核局部化的作用.
- 区分核张力依赖和控制YAP局部化的独立途径,以响应矩阵刚度.
主要方法:
- 在纤维细胞和人类介质干细胞 (hMSCs) 中利用了遗传和药理学抑制.
- 研究了粘附于可变形基质的细胞,以模仿不同的矩阵刚度.
- 评估了破坏温林-塔林和塔林-FAK相互作用对YAP定位,核大小和细胞引力的影响.
主要成果:
- 破坏素-素结合或降低素-1水平降低了核大小,引力和YAP核定位.
- 相比之下,破坏塔林与FAK的结合或抑制FAK的催化活性可以阻止YAP的核定位和活动,而不会改变核大小.
- 这些发现表明,矩阵刚度调节的YAP核定位有不同的机制.
结论:
- 在焦点粘附中,素-氨酸-FAK相互作用对于控制YAP核定位和转录活动至关重要.
- 数据支持模型涉及在矩阵刚度介导的YAP调节中的核张力依赖和独立路径.
- 突出了FA组件在控制YAP活动的机械传导通路中的复杂相互作用.
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